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Until now, scientists believed that only one type of immune cell could initiate the response. But a study from Washington University in St. Louis shows that even in the absence of this cell, the vaccine triggers a strong antitumor activity in mice.
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Mrna vaccines work by providing genetic instructions to our cells. These cells produce small protein fragments that alert the immune system. Dendritic cells present these fragments to T lymphocytes, which then eliminate the target cells. In cancer vaccines, these proteins mimic tumor markers. Until now, it was thought that only cDC1-type dendritic cells could activate T lymphocytes.
The research team worked with genetically modified mice. Some lacked cDC1 cells, others lacked cDC2 cells. To their great surprise, mice without cDC1 still developed a strong immune response after mRNA vaccination. They even managed to eliminate tumors. This indicates that cDC2 cells can compensate for the absence of cDC1. An unexpected result.
How do cDC2 cells activate T lymphocytes? The study reveals an indirect process called "cross-dressing." cDC2 cells do not produce the protein fragments themselves. They rely on other cells to process the mRNA and display the fragments on their surface. These fragments can then stimulate T lymphocytes.
The implications for designing cancer vaccines are promising. T lymphocytes activated by cDC1 and cDC2 carry slightly different molecular "fingerprints." According to the researchers, this signature could help optimize formulations and doses for future vaccines.
Mrna vaccines are already being tested against melanoma, lung, bladder, and other cancers. William Gillanders, co-author, notes that this work unveils a new way in which mRNA vaccines engage the immune system. Far from being a simple backup plan, the activation pathway via cDC2 appears to be a full component of the immune response. Scientists now plan to exploit this flexibility to create more effective vaccines.